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Geneticists home in on what makes us unique

As a parent who has logged more than my share of frustrating hours with the 'I Spy' series of books my kids love, I've learned that it doesn't matter how hard you look for something, if you're not looking in the right place you're not going to find it.

That's the take-home message from two recent papers by geneticist Michael Snyder, PhD. Snyder, who chairs Stanford's genetics department, and his colleagues showed that most human variation arises from differences in the DNA sequences that surround genes, rather than in the genes themselves. Small changes in the DNA sequence or structure of these regions affects how proteins called transcription factors bind and control the expression of downstream genes, says Snyder. These interactions ultimately play a larger role in individual variation (think appearance, predisposition to certain diseases, etc) than do the coding portions of our genome:

We are rapidly entering a time when nearly anyone can have his or her genome sequenced. However, the bulk of the differences among individuals are not found in the genes themselves, but in regions we know relatively little about. Now we see that these differences profoundly impact protein binding and gene expression.

Therefore, researchers who focus exclusively on genes to explain why individual humans differ are likely missing the boat (or, in my own little circle of I Spy hell, that dumb anchor on the island with the lighthouse and the treasure map). The papers, in Science Express and Nature describe how the researchers used humans, a chimpanzee and yeast to draw their conclusions.

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